2021 Grantee: Catherine F. Whittington, PhD
Worcester Polytechnic Institute
Research Project: Fibrosis-mediated Transformation in Pancreatic Cancer Risk Factors In Vitro
Award: 2021 Pancreatic Cancer Action Network Career Development Award
Award Period: July 1, 2021 – June 30, 2023
Dr. Catherine F. Whittington is an Assistant Professor of Biomedical Engineering at Worcester Polytechnic Institute (WPI). She is from Hallsville, TX, and received her BS in Biomedical Engineering in 2006 from Louisiana Tech University. She received her PhD in Biomedical Engineering in 2012 from Purdue University, and there she studied the effects of type I collagen mechanics and microstructure on capillary formation for wound healing applications.
After receiving her PhD, Dr. Whittington joined Eli Lilly and Company in Indianapolis, IN, as a Lilly Innovation Postdoctoral Research Fellow. This fellowship program promoted academic-industrial partnerships, and Dr. Whittington continued to work closely with Purdue. At Eli Lilly, she was in the Cancer Cell Signaling group and focused on improving the design of 3D tumor models of colorectal and pancreatic cancer and integrating them into higher throughput and higher content analysis protocols.
At WPI, the Whittington Laboratory operates at the interface of engineering design and in vitro model development. They use biomaterials to capture complex changes observed in the tissue microenvironment during regeneration and disease progression, particularly metastatic cancers. In pancreatic cancer, the group focuses on how microenvironmental changes within and around pancreatic tissue, primarily resulting from fibrosis, drives tumor cell invasion and metastasis.
Although it’s recognized that obesity is a risk factor for developing pancreatic ductal adenocarcinoma, the most common form of pancreatic cancer, it is still difficult to determine which patients will develop cancer. Currently, the disease is studied in the lab using cells grown in dishes or in animals, but few models effectively incorporate relevant features of risk factors.
Dr. Catherine F. Whittington proposes developing a cell-biomaterial based in vitro (cells grown in dishes) model that includes features shared between obesity and pancreatic cancer, such as fibrosis (excess tissue deposits) and inflammation. Moreover, those features are known to contribute, in part, to transforming cells into small pre-cancerous lesions, which develop before pancreatic cancer. Dr. Whittington and her team are also interested in understanding how the activities of exosomes (small particles that carry signals between cells) change in these different conditions and contribute to transformation.
The overall objective is to use their model to understand more about what makes obesity a risk factor for pancreatic cancer. The model will mimic the “stiffness” changes in pancreatic tumors caused by fibrosis and will include normal or cancer cells of the pancreas in addition to adipose (fat) cells. The research team will modify normal pancreatic cells to have one or two genetic mutations found in pancreatic cancer and evaluate for evidence of transformation and comparisons to cancer cells. All cells will be evaluated for changes in exosome production and uptake. Cells will then be cross-exposed to exosomes from other cell populations or grown together to show how fibrosis may play a role in altering adipose and pancreatic cell sensitivity to exosomes.
Overall, this work offers an innovative approach to modeling pancreatic cancer in the lab to understand the relationship between risk factors and pancreatic cancer development. Dr. Whittington’s team hopes to use their findings to create more predictive in vitro models that drive the system toward early lesion formation so they can identify potential markers for earlier detection of pancreatic cancer and/or develop new treatment strategies for high-risk individuals.